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An engineered VSV-vectored rabies vaccine with an RABV-G-L71S mutation
Mingxi Yue1,2, Yuhe Zhu1,2, Hongchao Wu3,4
1State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Science, Xiamen University, Xiamen, Fujian 361102, China.
Iscience
|November 28, 2025
Summary
A novel rabies vaccine candidate, rVSV-RABV-L71S, shows enhanced production and immunogenicity. This low-cost vaccine offers robust protection and favorable safety, making it ideal for global use.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Rabies remains a significant global health threat, necessitating effective and accessible vaccines.
- Recombinant vesicular stomatitis virus (VSV) vectors offer a promising platform for vaccine development.
- Enhancing viral titer and glycoprotein expression is crucial for vaccine efficacy.
Purpose of the Study:
- To construct and characterize a recombinant rabies vaccine expressing enhanced rabies virus glycoprotein (RABV-G).
- To evaluate the immunogenicity and protective efficacy of inactivated and live rVSV-RABV-L71S vaccine formulations.
- To assess the safety profile of the novel rabies vaccine candidate.
Main Methods:
- Construction of a recombinant VSV expressing RABV-G with a specific L71S mutation.
- Production and characterization of viral titers and G protein expression.
- Immunization of mice and dogs with inactivated and live vaccine formulations.
- Assessment of neutralizing antibody responses, T cell immunity, and challenge protection.
Main Results:
- The L71S mutation significantly enhanced viral titer and RABV-G expression.
- Inactivated rVSV-RABV-L71S with GEL-02 adjuvant induced superior antibody and T cell responses in mice compared to commercial vaccines.
- Live rVSV-RABV-L71S provided robust protection in mice and elicited strong neutralizing antibodies in dogs.
- Both vaccine formulations demonstrated favorable safety profiles.
Conclusions:
- rVSV-RABV-L71S exhibits significant production and immunogenic advantages.
- The vaccine candidate confers robust protection and elicits strong immune responses in preclinical models.
- rVSV-RABV-L71S is a promising, low-cost, high-efficacy rabies vaccine candidate for global deployment.
